Simple ruthenium complexes have proven highly productive in delineating and probing both the structural interactions and subsequent chemical, electrochemical and biochemical effects generated by metal-ion coordination to nucleic acids, their constituent bases, and redox-active coenzymes. New, sensitive electrochemical methods will now be used to probe differences in the electron transfer reactivity of DNA-coordinated metal ions and derivatized electrodes will be employed to extend the lower limits of these techniques. Electrode modifications will also be sought to begin the development of solid state DNA cleaving methods. Bis-intercalating complexes containing Tc will be developed to broaden the range of structural features available for binding to DNA. Complexes containing 99mTc, which is the most widely used radionuclide in diagnostic nuclear medicine, capable of binding to DNA should prove useful in the diagnosis of diseases affecting genetic material. Families of asymmetric and dissymmetric MU-oxo Tc complexes, containing the Tc atoms at a separation equal to that of DNA base-pairs, will be prepared with ligands on each Tc capable of intercalation and hydrogen-bonding to DNA bases so as to allow either bis-intercalation by the ligands or both intercalation of a ligand on one metal ion and covalent binding by the other. The mechanism of formation of these complexes will be studied in order to increase reaction efficiency at low Tc concentrations and to extend its synthetic versatility. Complexes will be characterized by conventional methods and as to their affinity for DNA and propensity for DNA unwinding. Selected agents will be tested in animal systems for tumor localization. Studies on the metal-catalyzed oxidation of nucleosides and ascorbate ion, and the effect of metal ion coordination of the electrochemical properties of pterins, will also be completed.